Colorectal cancer (CRC) is associated with one of the highest rates of mortality among cancers worldwide. The early detection and management of CRC is imperative. Biomarkers play an important role in CRC screening tests, CRC treatment, and prognosis and clinical management; thus rapid and sensitive detection of biomarkers is helpful for early detection of CRC. In recent years, electrochemical biosensors for detecting CRC biomarkers have been widely investigated. In this review, different electrochemical detection methods for CRC biomarkers including immunosensors, aptasensors, and genosensors are summarized. Further, representative examples are provided that demonstrate the advantages of electrochemical sensors modified by various nanomaterials. Finally, the limitations and prospects of biomarkers and electrochemical sensors in detection are also discussed. Graphical abstract.

In this study, we report an enzyme-free and conjugation-free electrochemical genosensor enabling an ultrasensitive readout of BRCA-1, a breast cancer susceptibility gene. The sensor employs a target-responsive hybridization chain reaction (HCR) to significantly amplify the detectable current signals. By means of a functional auxiliary probe pair and a versatile initiator sequence, a linear DNA concatemer structure can be formed via spontaneous and continuous polymerization of DNA oligomers in the presence of target sequence. Such a DNA nanoassembly endows the genosensor an ultrahigh sensitivity up to 1 aM, which is higher than that of the nanomaterials-based or enzyme mediated amplification approaches by several orders of magnitude. More importantly, the sensor\'s responsive peak current exhibits a favorable linear correlation to the logarithm of the concentrations of target sequence ranging from 1 aM to 10 pM. In addition, the sensor is highly selective, and can discriminate a single mismatched sequence. This HCR-based genosensor is also capable of probing low-abundance BRCA-1 gene sequence directly in complex matrices, such as 50% human serum, with minimal interference. These advantages will make our tailor-engineered HCR-based electrochemical genosensor appealing to genetic analysis and clinical diagnostics.